title: Inhibition of the Ca(2+)-sensing receptor rescues pulmonary hypertension in rats and mice.
abstract: A recent study from our group demonstrated that the Ca(2+)-sensing receptor (CaSR) was upregulated, and the extracellular Ca(2+)-induced increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was enhanced in pulmonary arterial smooth muscle cells from patients with idiopathic pulmonary arterial hypertension and animals with experimental pulmonary hypertension (PH). However, it is unclear whether CaSR antagonists (for example, NPS2143) rescue the development of experimental PH. We tested the rescue effects of NPS2143 in rats with monocrotaline (MCT)-induced PH and mice with chronic hypoxia-induced PH. For the NPS2143 treatment group, rats and mice were i.p. injected with NPS2143 once per day from days 14 to 24. Four weeks after MCT injection or exposure to normobaric hypoxia, the right ventricular (RV) systolic pressure, right heart hypertrophy (RV/LV+S ratio) and RV myocardial fibrosis were rescued or nearly restored to normal levels by NPS2143 treatment. The rescue effects of NPS2143 on experimental PH further support a critical role for the CaSR in the PH mechanism. Therefore, NPS2143 may be a promising potential treatment for pulmonary arterial hypertension.
authors.affiliation: Department of Medicine, Respiratory, Infectious, Emergency and Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Medicine, Respiratory, Infectious, Emergency and Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Huang
authors.affiliation: 1] Section of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Medicine, Institute for Personalized Respiratory Medicine, Chicago, IL, USA [2] Department of Pharmacology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Yamamura
authors.affiliation: 1] Section of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Medicine, Institute for Personalized Respiratory Medicine, Chicago, IL, USA [2] Department of Pharmacology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Hisao
authors.initials: H
authors.lastname: Yamamura
authors.affiliation: 1] Section of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Medicine, Institute for Personalized Respiratory Medicine, Chicago, IL, USA [2] Department of Pharmacology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Zimnicka
authors.affiliation: 1] Section of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Medicine, Institute for Personalized Respiratory Medicine, Chicago, IL, USA [2] Department of Pharmacology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Ruby
authors.initials: R
authors.lastname: Fernandez
authors.affiliation: 1] Section of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Medicine, Institute for Personalized Respiratory Medicine, Chicago, IL, USA [2] Department of Pharmacology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jason X-J
authors.initials: JX
authors.lastname: Yuan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016686:Monocrotaline; D009206:Myocardium / Q000473:pathology; D011042:Poisons; D011651:Pulmonary Artery / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D011042:Poisons; D044169:Receptors, Calcium-Sensing; D016686:Monocrotaline; D002118:Calcium